Beta-adrenergic receptor antagonists(β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol...Beta-adrenergic receptor antagonists(β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol, metoprolol and carvedilol have been in clinical practice in patients with cirrhosis. Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor blocker in trials conducted testing its efficacy for heart failure. Whether the same effect extends to its potency in the reduction of portal venous pressures is a topic of on-going debate. The aim of this review is to compare the hemodynamic and clinical effects of carvedilol with propranolol, and attempt assess whether carvedilol can be used instead of propranolol in patients with cirrhosis. Carvedilol is a promising agent among the beta blockers of recent time that has shown significant effects in portal hypertension hemodynamics. It has also demonstrated an effective profile in its clinical application specifically for the prevention of variceal bleeding. Carvedilol has more potent desired physiological effects when compared to Propranolol. However, it is uncertain at the present juncture whether the improvement in hemodynamics also translates into a decreased rate of disease progression and complications when compared to propranolol. Currently Carvedilol shows promise as a therapy for portal hypertension but more clinical trials need to be carried out before we can consider it as a superior option and a replacement for propranolol.展开更多
AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic microsomes.METHODS Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF an...AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic microsomes.METHODS Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF and PB and the non-induced microsome asthe control.The enzymatic kinetic parameters ofpropranolol enantiomers were calculated byregression analysis of Lineweaver-Burk plots.Propranolol concentrations were assayed byHPLC.RESULTS A RP-HPLC method was developed todetermine propranolol concentration in rathepatic microsomes.The linearity equations forR（+）-propranolol and S（-）-propranolol wereA=705.7C+311.2C（R = 0.9987）and A= 697.2C+311.4C（R = 0.9970）respectively.Recoveriesof each enantiomer were 98.9%,99.5%,101.0%at 60 μmol/L,120 μmol/L,240 μmol/Lrespectively.At the concentration level of120 μmol/L,propranolol enantiomers weremetabolized at different rates in differentmicrosomes.The concentration ratio R（+）/S（-）of control and PB induced microsomesincreased with time,whereas that of microsomeinduced by BNF decreased.The assayed enzymeparameters were:1.Km.Control group:R（+）30+<sub>8</sub>,S（-）18+<sub>5</sub>;BNFgroup:R（+）34+3,S（-）39±7;PB group:R（+）38±17,S（-）36±10.2.Vmax.Control group:R（+）1.5+0.2,S（-）2.9±0.3;BNF group:R（+）3.8±0.3,S（-）3.3±0.5;PB group:R（+）0.07±0.03,S（-）1.94±0.07.3.Clint.Control group:R（+）60±3,S（-）170±30;BNF group:R（+）111.0±1,S（-）84± 5;PBgroup:R（+）2.0±2,S（-）56.0±1.Theenzyme.parameters compared with unpaired ttests showed that no stereoselectivity wasobserved in enzymatic affinity of threemicrosomes to enantiomers and their catalyticabilities were quite different and hadstereoselectivities.Compared with the control,microsome induced by BNF enhanced enzymeactivity to propranolol R（+）-enantiomer,andmicrosome induced by PB showed less enzymeactivity to propranolol S（-）-enantiomer whichremains the same stereoselectivities as that ofthe control.CONCLUSION Enzyme activity centers of themicrosome were changed in composition andregioselectivity after the induction of BNF andPB,and the stereoselectivities of propranololcytochrome P450 metabolism in rat hepaticmicrosomes were likely due to thestereoselectivities of the catalyzing function inenzyme.CYP1A subfamily induced by BNFexhibited pronounced contribution to propranololmetabolism with stereoselectivity to R（+）-enantiomer.CYP2B subfamily induced by PBexhibited moderate contribution to propranololmetabolism,but still had the stereoselectivity ofS（-）-enantiomer.展开更多
AIM: To compare the effects of propranolol (PR) to that of PR plus isosorbide-5-mononitrate (ISMN) on variceal pressure in patients with schistosomiasis. METHODS: Forty-eight patients with schistosomiasis who had no p...AIM: To compare the effects of propranolol (PR) to that of PR plus isosorbide-5-mononitrate (ISMN) on variceal pressure in patients with schistosomiasis. METHODS: Forty-eight patients with schistosomiasis who had no previous variceal bleeding were treated with PR alone or PR plus ISMN. Seven patients refused variceal pressure manometry (3 receiving PR and 4 receiving PR plus ISMN). One patient withdrew from the trial due to headache after taking ISMN. At the time of termination, twenty patients were randomly assigned to treatment with PR plus ISMN or PR alone. The dose of PR was adjusted until the resting heart rate had been reduced by 25% or was less than 55 bpm. In the PR plus ISMN group, after PR was titrated to the same target, the dose of ISMN was increased up to 20 mg orally twice a day. Variceal pressure was measured using a noninvasive endoscopic balloon technique at the end of the 6-mo treatment period. RESULTS: In 40 patients (20 in the PR group and 20 in the PR plus ISMN group), variceal pressure was measured before treatment and at the end of the 6-mo treatment period. PR or PR plus ISMN treatment caused a significant reduction in variceal pressure (PR group: from 24.15 ± 6.05 mmHg to 22.68 ± 5.70 mmHg, P = 0.001; PR plus ISMN group: from 25.69 ± 5.26 mmHg to 20.48 ± 5.43 mmHg; P < 0.001). The percentage decrease in variceal pressure was significant after PR plus ISMN compared with that after PR alone (15.93% ± 8.37% vs 6.05% ± 3.67%, P = 0.01). One patient in the PR plus ISMN group and two patients in the PR group had variceal bleeding during follow-up. There were no significant differences between the two groups regarding the incidence of variceal bleeding. In the PR plus ISMN group, three patients had headache and hypotension. The headache was mild and transient and promptly disappeared after continuation of the relevant drug in two patients. Only one patient withdrew from the trial due to severe and lasting headache after taking ISMN. No side effects occurred in the PR group. CONCLUSION: PR plus ISMN therapy may be an alternative treatment for patients with schistosomiasis who have a high risk of bleeding.展开更多
AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in ...AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β 2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients.RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively.Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes(22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%,respectively, P < 0.01).CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β 2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy.展开更多
AIM: To investigate the effects of periocular injection of propranolol and celecoxib on ocular levels of vascular endothelial growth factor(VEGF) in a diabetic mouse model.METHODS: Forty 4-6wk BALB-C male mice weighin...AIM: To investigate the effects of periocular injection of propranolol and celecoxib on ocular levels of vascular endothelial growth factor(VEGF) in a diabetic mouse model.METHODS: Forty 4-6wk BALB-C male mice weighing20-25 g were used. The study groups included: non-diabetic control(group 1), diabetic control(group 2),diabetic propranolol(group 3), and diabetic celecoxib(group 4). After induction of type 1 diabetes by streptozotocin, propranolol(10 μg) and celecoxib(200 μg dissolved in carboxymethylcellulose 0.5%) were injected periocularly. The ocular level of VEGF was measured in all the study groups using enzyme-linked immuno sorbent assay(ELISA) method. RESULTS: Ocular VEGF level was significantly increased(1.25 fold) in the diabetic control group when compared to the non-diabetic group one week after induction with streptozotocin(P =0.002). Both periocular propranolol and celecoxib significantly reduced ocular VEGF levels(P =0.047 and P <0.001, respectively). The effect was more pronounced with celecoxib. CONCLUSION: The periocular administration of propranolol and celecoxib can significantly reduce ocular VEGF levels in a diabetic mouse model.展开更多
The clinical efficacy and safety of topical propranolol hydrochloride gel in the treatment of superficial infantile hemangiomas (IHs) were assessed. Fifty-one cases of IHs from Oct. 2010 to Sept. 2011 were subjected t...The clinical efficacy and safety of topical propranolol hydrochloride gel in the treatment of superficial infantile hemangiomas (IHs) were assessed. Fifty-one cases of IHs from Oct. 2010 to Sept. 2011 were subjected to the topical propranolol hydrochloride gel intervention in Fuzhou General Hospital of Nanjing Military Commands, China. Changes in size, texture, color, peak systolic velocity of the hemangiomas, resistance index and adverse effects were observed. The results were evaluated by using Achauer system, and responses of IHs to pranpronolol were considered scaleⅠ(poor) in 4 patients (17.24%), scaleⅡ(moderate) in 18 patients (24.14%), scale Ⅲ (good) in 22 patients (44.83%) and scale Ⅳ (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P<0.05), and no differences in response were found among different primary sites (P>0.05). Our study indicates that topical application of 3% propranolol hydrochloride gel is effective and safe in treating IHs.展开更多
The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve perm...The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve permeability of drugs that undergo firstpass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL(70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles(PN-films) and HPMC/PC blend films containing PNL(80 mg/film) without nanoparticles(PPfilms) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope(SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film(PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index(SI)of all PN-films and PP-films increased greatly in the first period time(10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points(10–30 min). After 120 min, the release of PN-films-70 was lower than the other PNfilms. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.展开更多
Infantile hemangioma(IH) is the most common benign tumor seen in infancy. This review provides up-to-date information on the pathophysiology, variations in clinical presentation, and natural history of IH, elaborating...Infantile hemangioma(IH) is the most common benign tumor seen in infancy. This review provides up-to-date information on the pathophysiology, variations in clinical presentation, and natural history of IH, elaborating on associated anomalies, such as PHACE(S) syndrome and LUMBAR syndrome. Because of the benign and self-limiting characteristics seen in more than 90% of cases of IH, a conservative approach is usually chosen. However, some circumstances, such as ulceration, vision loss, breathing difficulties, or potential disfigurement, will require treatment during the proliferative phase. For decades, treatment of IH has primarily consisted of corticosteroids or surgery. Since 2008, propranolol has become the treatment of first choice. In this article, we bring to light the crucial changes in the treatment of IH over the past years. To date, there is still a lack of data on the possible long-term effects of propranolol treatment in young infants. A theoretical probability of the central nervous system being affected(that is, impairment of short- and long-term memory, psychomotor function, sleep quality, and mood) has recently been suggested. This review highlights research topics concerning these long-term adverse effects. Finally, information is provided on the potential instruments to measure IH severity and activity in clinical trials and/or in clinical practice and the recently developed and first-validated IH-specific quality-of-life questionnaire.展开更多
Infantile hemangioma (IH) is a common tumor in infants. After the proliferative phase, hemangiomas regress, but sometimes leave scars. Propranolol is now the recommended first-line oral therapy for IH. To evaluate the...Infantile hemangioma (IH) is a common tumor in infants. After the proliferative phase, hemangiomas regress, but sometimes leave scars. Propranolol is now the recommended first-line oral therapy for IH. To evaluate the effectiveness of oral propranolol administration, we measured quantitative changes in an IH by digital camera and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Although digital cameras are very simple, changes in color tones occur with time, lesions are evaluated in two dimensions, and changes in the thickness of the hemangioma are difficult to evaluate. Therefore, we investigated the feasibility of 3D photography to quantify volumes in IH during oral propranolol treatment.展开更多
By using receptor autoradiography to observe the distribution and density of receptors, the effects of propranolol, a β-blocker, on β-adrenergic receptor of experimental acute myocardial infarction (AMI) were studie...By using receptor autoradiography to observe the distribution and density of receptors, the effects of propranolol, a β-blocker, on β-adrenergic receptor of experimental acute myocardial infarction (AMI) were studied. One week after ligation of proximate left anterior descend (LAD) coronary artery, [3H] DHA binding sites were markedly decreased in both infarctregion and non-infarct region. After treatment of propranolol (100μg/kg), the [3H] DHA binding sites were obviously increased in the infarct region, and they were further decreased in the non-infarct region. The ratio of [3H] DHA binding sites of the infarct region to non-infarct region was from 0. 24 at LAD ligation to 0. 87 after propranolol treatment, which was close to 0. 97 of control group (sham operation). The results indicated that the propranolol acted directly on myocardial β-adrenergic through the receptor regulation of the balance of β-receptors between the infarct region and non-infarct region, and improvement of the myocardial consonation and contraction synergism, thereby protecting the heart affected by AMI.展开更多
Purpose: Investigating the triple effect of doxorubicin, 5-fluorouracil, propranolol on MCF-7 (ER+, WTp53) breast cancer cell line with MTT test and survival analysis. Materials/Methods: In order to determine effectiv...Purpose: Investigating the triple effect of doxorubicin, 5-fluorouracil, propranolol on MCF-7 (ER+, WTp53) breast cancer cell line with MTT test and survival analysis. Materials/Methods: In order to determine effective dosages of a combination of doxorubicin, 5-fluorouracil, propranolol on the MCF-7 cell line by using MTT and survival analysis technique. Result: IC50 values acquired by MTT tests are 0.01 mg/ml for doxorubicin, 6 mg/ml for 5-fluorouracil, 30 mg/ml for propranolol and 0.2/1/30 mg/ml (with previous respect) if all three agents are combined. It is found that the use of doxorubicin, 5-fluorouracil, and propranolol in combination is much effective than their single application. Discussion: Moderate concentrations of doxorubicin, 5-fluorouracil, and propranolol, if they are applied individually, showed high toxicity. When we used these drugs in combination;toxic effects lessened with respect to monotherapy. In the MCF-7 cell line, doxorubicin (IC50: 0.01 μM) increases cell death rates significantly and propranolol (IC50: 3 μM) has minimum effects in monotherapy in contrast to others. Propranolol is only superior to itself in combination therapy (IC50: 4 μM). However 5-fluorouracil (IC50: 30 μM) showed antagonistic effects with respect to other drugs. Additionally, having applied the three drugs in combination on the MCF-7 cell line for the first time in literature, it is highly possible to assess the application of doxorubicin, 5-fluorouracil and propranolol combination as a novel therapy option.展开更多
Background: Infantile haemangioma is the commonest childhood tumor. Several lines of treatment are available. Recent reports have focused on the value of propranolol in treating rapidly proliferating haemangioma. The ...Background: Infantile haemangioma is the commonest childhood tumor. Several lines of treatment are available. Recent reports have focused on the value of propranolol in treating rapidly proliferating haemangioma. The aim of this study was to assess oral propranolol in treatment for facial haemangioma. Patients and Methods: Fifteen patients with rapidly proliferating infantile facial haemangioma with cosmetic disfigurement were treated with oral propranolol. All patients had cardiovascular pre-treatment work-up and commenced on oral propranolol at 3 mg/kg/day. Results: A rapid decrease in hemangioma proliferation was seen in 100% of patients and significant regressions occuring in all patients. This treatment was well tolerated and had little side effects. Conclusions: Oral propranolol is a reliable and easily reproducible method for treatment of facial hemangioma.展开更多
Infantile hemangioma and burn hemangioma have many similarities in clinical pictures, pathology and treatment. As infantile hemangioma appears usually after birth and then rapidly grow within few months and then a sta...Infantile hemangioma and burn hemangioma have many similarities in clinical pictures, pathology and treatment. As infantile hemangioma appears usually after birth and then rapidly grow within few months and then a statue state and then involutes within few years while burn hemangioma so called burn pyogenic granuloma usually appears within days after burn with liquid and grow rapidly into many giant angiomatous masses and then after short time usually weeks or months will involute in more than 37.5% of cases. Hence burn hemangioma and infantile hemangioma sharing many similar features as both are angiomatous with dramatic rapid proliferation of blood vessels that followed by involution but with different time periods and both carry CD133 and CD34 for infantile hemangioma and CD34 for burn hemangioma. Also infantile hemangioma rapidly responds to systemic propranolol and similarly do in cases of burn hemangioma. Accordingly it is more better scientifically to call scalded pyogenic granuloma burn hemangioma. The objective of the present report is to review these conditions and do comparison between them and also to record 6 cases of burn hemangioma and its effective therapy with oral propranolol.展开更多
Kaposi’s sarcoma (KS) in Iraq has been reported as sporadic cases of elderly of Iraqi population but after exposure to depleted uranium radiation in early 1991, the frequency of the disease is increasing appearing in...Kaposi’s sarcoma (KS) in Iraq has been reported as sporadic cases of elderly of Iraqi population but after exposure to depleted uranium radiation in early 1991, the frequency of the disease is increasing appearing in younger age with more wide spread and aggressive in nature. There is no satisfactory oral treatment to control this disease. The aim of the present work is to record a new regime of therapy using oral zinc sulfate and oral propanolol. Four patients with wide spread Kaposi’s sarcoma (KS) were treated with oral and topical zinc sulfate solution and oral propranolol. The duration of treatment was between 6 - 12 months and the response started few weeks and was obvious after one month. Most old lesions were resolved leaving post inflammatory hyperpigmentation and few lesions appeared during course of treatment.展开更多
The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method...The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method and the change of heart rate was evaluated by ECG. Both isomers of propranolol hydrochloride were administered iv （800 μg/kg） to the rabbits. d-propranolol produced an antipyrine t 1/2 of 2.67±0.77h and a cl of 0.49±0.1 l/h while its levo-form produced an antipyrine t 1/2 of 1.7±0.39h and a cl of 0.88±0.22 l/h. The differences between the half-lives and between the clearances were statistically significant （P【0.05 for t 1/2, P【0.01 for cl）. The inhibitory effects of l- and d-propranolol on isoprenaline-induced tachycardia were assessed. l-propranolol yielded an ID<sub>50</sub> which was only 1/88 of d-propranolol’s. Our studies showed that the β-receptor blocking activity of propranolol mainly came. from its levoform while the effect on antipyrine metabolism came from its dextro-form.展开更多
Epistaxis is a common complaint which is rarely life-threatening, as most cases are self-limited and as such unreported. However, it may be a significant cause for concern if it becomes recurrent. Although a number of...Epistaxis is a common complaint which is rarely life-threatening, as most cases are self-limited and as such unreported. However, it may be a significant cause for concern if it becomes recurrent. Although a number of medications including topical antihistamines and non-steroidal anti-inflammatory drugs are known aetiological factors for epistaxis due to their antiplatelet effects, beta blockers are not being widely reported as a possible cause. This report presents the case of a 34-year-old G2P0+1, who was diagnosed with hyperthyroidism in pregnancy and subsequently reported epistaxis twice at different occasion and different hospital settings when propranolol was introduced for her treatment, with resolution of epistaxis after withdrawal of propranolol. The report aims to highlight and sensitize physicians to the possible risk of bleeding in patients placed on beta blockers especially propranolol for a wide range of medical condition due to its thrombocytopathic effect.展开更多
AIM: To study the stereoselectivity of phase Ⅱglucuronidation metabolism of side-chain propranolol in Chinese Hah population.METHODS: Sixteen adult Chinese Hah volunteers with an average age of 20 years were given a ...AIM: To study the stereoselectivity of phase Ⅱglucuronidation metabolism of side-chain propranolol in Chinese Hah population.METHODS: Sixteen adult Chinese Hah volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC.RESULTS: The mean values of kwere 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of doses were 14.7±2.46% and 7.68±1.60% for S-(-)- and R-(+)-propranolol glucuronide,respectively. The results showed the elimination rate constant kof S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide.CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.展开更多
Objective: This study was originally designed to observe the effects of propranolol (a β-blocker) and Zhigancao Decoction (炙甘草汤 ZGCD) on bone mass in ovariectomized rats. Methods: Thirty-eight female Sprague-Dawl...Objective: This study was originally designed to observe the effects of propranolol (a β-blocker) and Zhigancao Decoction (炙甘草汤 ZGCD) on bone mass in ovariectomized rats. Methods: Thirty-eight female Sprague-Dawley rats were divided into four groups initially, a sham-operated group (Sham, n=7), a model ovariectomized (OVX) group (Model, n=7), a propranolol group (Pro, n=12) and a ZGCD group (ZGCD, n=12). After 15 weeks of treatment, the expected effects were not found. In order to verify the situations of the experiment, we modified the study by administering calcitonin to a subgroup of the tested Pro and ZGCD rats. Results: The Pro and ZGCD treatments showed decreased heart rate and plasma norepinephrine level, but neither an increased bone mass nor any bone metabolism differences from the model rats were found. However, the OVX-induced bone loss was prevented by the sequent treatment of calcitonin. Conclusions: The results provide no evidence that the β-blocker propranolol may stimulate bone formation, and do not justify its use for clinical treatment of osteoporosis.展开更多
文摘Beta-adrenergic receptor antagonists(β-blockers) have been well established for use in portal hypertension for more than three decades. Different Non-selective β-blockers like propranolol, nadolol, timolol, atenolol, metoprolol and carvedilol have been in clinical practice in patients with cirrhosis. Carvedilol has proven 2-4 times more potent than propranolol as a beta-receptor blocker in trials conducted testing its efficacy for heart failure. Whether the same effect extends to its potency in the reduction of portal venous pressures is a topic of on-going debate. The aim of this review is to compare the hemodynamic and clinical effects of carvedilol with propranolol, and attempt assess whether carvedilol can be used instead of propranolol in patients with cirrhosis. Carvedilol is a promising agent among the beta blockers of recent time that has shown significant effects in portal hypertension hemodynamics. It has also demonstrated an effective profile in its clinical application specifically for the prevention of variceal bleeding. Carvedilol has more potent desired physiological effects when compared to Propranolol. However, it is uncertain at the present juncture whether the improvement in hemodynamics also translates into a decreased rate of disease progression and complications when compared to propranolol. Currently Carvedilol shows promise as a therapy for portal hypertension but more clinical trials need to be carried out before we can consider it as a superior option and a replacement for propranolol.
基金the National Natural Science Foundation of China,No.39370805.
文摘AIM To study the influence of inducers BNFand PB on the stereoselective metabolism ofpropranolol in rat hepatic microsomes.METHODS Phase Ⅰ metabolism of propranololwas studied by using the microsomes induced byBNF and PB and the non-induced microsome asthe control.The enzymatic kinetic parameters ofpropranolol enantiomers were calculated byregression analysis of Lineweaver-Burk plots.Propranolol concentrations were assayed byHPLC.RESULTS A RP-HPLC method was developed todetermine propranolol concentration in rathepatic microsomes.The linearity equations forR（+）-propranolol and S（-）-propranolol wereA=705.7C+311.2C（R = 0.9987）and A= 697.2C+311.4C（R = 0.9970）respectively.Recoveriesof each enantiomer were 98.9%,99.5%,101.0%at 60 μmol/L,120 μmol/L,240 μmol/Lrespectively.At the concentration level of120 μmol/L,propranolol enantiomers weremetabolized at different rates in differentmicrosomes.The concentration ratio R（+）/S（-）of control and PB induced microsomesincreased with time,whereas that of microsomeinduced by BNF decreased.The assayed enzymeparameters were:1.Km.Control group:R（+）30+<sub>8</sub>,S（-）18+<sub>5</sub>;BNFgroup:R（+）34+3,S（-）39±7;PB group:R（+）38±17,S（-）36±10.2.Vmax.Control group:R（+）1.5+0.2,S（-）2.9±0.3;BNF group:R（+）3.8±0.3,S（-）3.3±0.5;PB group:R（+）0.07±0.03,S（-）1.94±0.07.3.Clint.Control group:R（+）60±3,S（-）170±30;BNF group:R（+）111.0±1,S（-）84± 5;PBgroup:R（+）2.0±2,S（-）56.0±1.Theenzyme.parameters compared with unpaired ttests showed that no stereoselectivity wasobserved in enzymatic affinity of threemicrosomes to enantiomers and their catalyticabilities were quite different and hadstereoselectivities.Compared with the control,microsome induced by BNF enhanced enzymeactivity to propranolol R（+）-enantiomer,andmicrosome induced by PB showed less enzymeactivity to propranolol S（-）-enantiomer whichremains the same stereoselectivities as that ofthe control.CONCLUSION Enzyme activity centers of themicrosome were changed in composition andregioselectivity after the induction of BNF andPB,and the stereoselectivities of propranololcytochrome P450 metabolism in rat hepaticmicrosomes were likely due to thestereoselectivities of the catalyzing function inenzyme.CYP1A subfamily induced by BNFexhibited pronounced contribution to propranololmetabolism with stereoselectivity to R（+）-enantiomer.CYP2B subfamily induced by PBexhibited moderate contribution to propranololmetabolism,but still had the stereoselectivity ofS（-）-enantiomer.
基金Supported by Educational and Health Department of Anhui Province, No. KJ2010A158, KJ2012Z189, 2010B018General Program of National Natural Science Foundation of China, No.81070337, 81271736
文摘AIM: To compare the effects of propranolol (PR) to that of PR plus isosorbide-5-mononitrate (ISMN) on variceal pressure in patients with schistosomiasis. METHODS: Forty-eight patients with schistosomiasis who had no previous variceal bleeding were treated with PR alone or PR plus ISMN. Seven patients refused variceal pressure manometry (3 receiving PR and 4 receiving PR plus ISMN). One patient withdrew from the trial due to headache after taking ISMN. At the time of termination, twenty patients were randomly assigned to treatment with PR plus ISMN or PR alone. The dose of PR was adjusted until the resting heart rate had been reduced by 25% or was less than 55 bpm. In the PR plus ISMN group, after PR was titrated to the same target, the dose of ISMN was increased up to 20 mg orally twice a day. Variceal pressure was measured using a noninvasive endoscopic balloon technique at the end of the 6-mo treatment period. RESULTS: In 40 patients (20 in the PR group and 20 in the PR plus ISMN group), variceal pressure was measured before treatment and at the end of the 6-mo treatment period. PR or PR plus ISMN treatment caused a significant reduction in variceal pressure (PR group: from 24.15 ± 6.05 mmHg to 22.68 ± 5.70 mmHg, P = 0.001; PR plus ISMN group: from 25.69 ± 5.26 mmHg to 20.48 ± 5.43 mmHg; P < 0.001). The percentage decrease in variceal pressure was significant after PR plus ISMN compared with that after PR alone (15.93% ± 8.37% vs 6.05% ± 3.67%, P = 0.01). One patient in the PR plus ISMN group and two patients in the PR group had variceal bleeding during follow-up. There were no significant differences between the two groups regarding the incidence of variceal bleeding. In the PR plus ISMN group, three patients had headache and hypotension. The headache was mild and transient and promptly disappeared after continuation of the relevant drug in two patients. Only one patient withdrew from the trial due to severe and lasting headache after taking ISMN. No side effects occurred in the PR group. CONCLUSION: PR plus ISMN therapy may be an alternative treatment for patients with schistosomiasis who have a high risk of bleeding.
基金Supported by National Natural Science Foundation of China,No.81271736
文摘AIM: To evaluate the association of β-2 adrenergic receptor(β2-AR) gene polymorphism with response of variceal pressure to propranolol in cirrhosis.METHODS: Sixty-four non-related cirrhotic patients participated in this study and accepted variceal pressure measurement before and after propranolol administration. Polymorphism of the β 2-AR gene was determined by directly sequencing of the polymerase chain reaction products from the DNA samples that were prepared from the patients.RESULTS: The prevalence of Gly16-Glu/Gln27 and Arg16-Gln27 homozygotes, and compound heterozygotes was 29.7%, 10.9%, and 59.4%, respectively.Patients with cirrhosis with Gly16-Glu/Gln27 homozygotes had a greater decrease of variceal pressure after propranolol administration than those with Arg16-Gln27 homozygotes or with compound heterozygotes(22.4% ± 2.1%, 13.1% ± 2.7% and 12.5% ± 3.1%,respectively, P < 0.01).CONCLUSION: The variceal pressure response to propranolol was associated with polymorphism of β 2-AR gene. Patients with the Gly16-Glu/Gln27 homozygotes probably benefit from propranolol therapy.
基金Supported by the Ahvaz Jundishapur University of Medical Sciences(No.IORC-9203)
文摘AIM: To investigate the effects of periocular injection of propranolol and celecoxib on ocular levels of vascular endothelial growth factor(VEGF) in a diabetic mouse model.METHODS: Forty 4-6wk BALB-C male mice weighing20-25 g were used. The study groups included: non-diabetic control(group 1), diabetic control(group 2),diabetic propranolol(group 3), and diabetic celecoxib(group 4). After induction of type 1 diabetes by streptozotocin, propranolol(10 μg) and celecoxib(200 μg dissolved in carboxymethylcellulose 0.5%) were injected periocularly. The ocular level of VEGF was measured in all the study groups using enzyme-linked immuno sorbent assay(ELISA) method. RESULTS: Ocular VEGF level was significantly increased(1.25 fold) in the diabetic control group when compared to the non-diabetic group one week after induction with streptozotocin(P =0.002). Both periocular propranolol and celecoxib significantly reduced ocular VEGF levels(P =0.047 and P <0.001, respectively). The effect was more pronounced with celecoxib. CONCLUSION: The periocular administration of propranolol and celecoxib can significantly reduce ocular VEGF levels in a diabetic mouse model.
文摘The clinical efficacy and safety of topical propranolol hydrochloride gel in the treatment of superficial infantile hemangiomas (IHs) were assessed. Fifty-one cases of IHs from Oct. 2010 to Sept. 2011 were subjected to the topical propranolol hydrochloride gel intervention in Fuzhou General Hospital of Nanjing Military Commands, China. Changes in size, texture, color, peak systolic velocity of the hemangiomas, resistance index and adverse effects were observed. The results were evaluated by using Achauer system, and responses of IHs to pranpronolol were considered scaleⅠ(poor) in 4 patients (17.24%), scaleⅡ(moderate) in 18 patients (24.14%), scale Ⅲ (good) in 22 patients (44.83%) and scale Ⅳ (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P<0.05), and no differences in response were found among different primary sites (P>0.05). Our study indicates that topical application of 3% propranolol hydrochloride gel is effective and safe in treating IHs.
基金the financial support provided by Thammasat University under the TU Research Scholar,Contract No.TP 2/68/2556
文摘The aims of this study were to prepare and characterize hydroxypropyl methylcellulose(HPMC)/polycarbophil(PC) mucoadhesive blend films saturated with propranolol hydrochloride(PNL)-loaded nanoparticles to improve permeability of drugs that undergo firstpass metabolism. An ionic cross-linking method and film casting technique was used to prepare nanoparticles and mucoadhesive blend films, respectively. Increasing concentrations of PNL(70, 80, 90 mg/film) in HPMC/PC blend films containing PNL-loaded nanoparticles(PN-films) and HPMC/PC blend films containing PNL(80 mg/film) without nanoparticles(PPfilms) were prepared to test swelling, mucoadhesiveness, release, permeation and physicochemical properties. Scanning electron microscope(SEM) images showed a partially smooth surface with a wrinkled occurrence and spherically shaped, well-dispersed nanoparticles on the surface of PN-films containing PNL 80 mg/film(PN-films-80). The size of the nanoparticles on the surface of PN-films-80 was around 100 nm, which was similar to the nanoparticle size observed using light scattering technique. The swelling index(SI)of all PN-films and PP-films increased greatly in the first period time(10–20 min) and reached swelling equilibrium at 20 min and 30 min, respectively. For the PN-films, the concentration of PNL influenced the mucoadhesive properties and tended to be higher when the amount of PNL increased. Immediate release of all blend film formulations was found in early time points(10–30 min). After 120 min, the release of PN-films-70 was lower than the other PNfilms. Permeation studies using porcine buccal mucosa showed that inclusion of nanoparticles in the films increased the permeability of PNL compared to PP-films. Therefore, buccal administration of mucoadhesive blend films containing PNL-loaded nanoparticles could be a promising approach for drugs that undergo first-pass metabolism.
文摘Infantile hemangioma(IH) is the most common benign tumor seen in infancy. This review provides up-to-date information on the pathophysiology, variations in clinical presentation, and natural history of IH, elaborating on associated anomalies, such as PHACE(S) syndrome and LUMBAR syndrome. Because of the benign and self-limiting characteristics seen in more than 90% of cases of IH, a conservative approach is usually chosen. However, some circumstances, such as ulceration, vision loss, breathing difficulties, or potential disfigurement, will require treatment during the proliferative phase. For decades, treatment of IH has primarily consisted of corticosteroids or surgery. Since 2008, propranolol has become the treatment of first choice. In this article, we bring to light the crucial changes in the treatment of IH over the past years. To date, there is still a lack of data on the possible long-term effects of propranolol treatment in young infants. A theoretical probability of the central nervous system being affected(that is, impairment of short- and long-term memory, psychomotor function, sleep quality, and mood) has recently been suggested. This review highlights research topics concerning these long-term adverse effects. Finally, information is provided on the potential instruments to measure IH severity and activity in clinical trials and/or in clinical practice and the recently developed and first-validated IH-specific quality-of-life questionnaire.
文摘Infantile hemangioma (IH) is a common tumor in infants. After the proliferative phase, hemangiomas regress, but sometimes leave scars. Propranolol is now the recommended first-line oral therapy for IH. To evaluate the effectiveness of oral propranolol administration, we measured quantitative changes in an IH by digital camera and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Although digital cameras are very simple, changes in color tones occur with time, lesions are evaluated in two dimensions, and changes in the thickness of the hemangioma are difficult to evaluate. Therefore, we investigated the feasibility of 3D photography to quantify volumes in IH during oral propranolol treatment.
文摘By using receptor autoradiography to observe the distribution and density of receptors, the effects of propranolol, a β-blocker, on β-adrenergic receptor of experimental acute myocardial infarction (AMI) were studied. One week after ligation of proximate left anterior descend (LAD) coronary artery, [3H] DHA binding sites were markedly decreased in both infarctregion and non-infarct region. After treatment of propranolol (100μg/kg), the [3H] DHA binding sites were obviously increased in the infarct region, and they were further decreased in the non-infarct region. The ratio of [3H] DHA binding sites of the infarct region to non-infarct region was from 0. 24 at LAD ligation to 0. 87 after propranolol treatment, which was close to 0. 97 of control group (sham operation). The results indicated that the propranolol acted directly on myocardial β-adrenergic through the receptor regulation of the balance of β-receptors between the infarct region and non-infarct region, and improvement of the myocardial consonation and contraction synergism, thereby protecting the heart affected by AMI.
文摘Purpose: Investigating the triple effect of doxorubicin, 5-fluorouracil, propranolol on MCF-7 (ER+, WTp53) breast cancer cell line with MTT test and survival analysis. Materials/Methods: In order to determine effective dosages of a combination of doxorubicin, 5-fluorouracil, propranolol on the MCF-7 cell line by using MTT and survival analysis technique. Result: IC50 values acquired by MTT tests are 0.01 mg/ml for doxorubicin, 6 mg/ml for 5-fluorouracil, 30 mg/ml for propranolol and 0.2/1/30 mg/ml (with previous respect) if all three agents are combined. It is found that the use of doxorubicin, 5-fluorouracil, and propranolol in combination is much effective than their single application. Discussion: Moderate concentrations of doxorubicin, 5-fluorouracil, and propranolol, if they are applied individually, showed high toxicity. When we used these drugs in combination;toxic effects lessened with respect to monotherapy. In the MCF-7 cell line, doxorubicin (IC50: 0.01 μM) increases cell death rates significantly and propranolol (IC50: 3 μM) has minimum effects in monotherapy in contrast to others. Propranolol is only superior to itself in combination therapy (IC50: 4 μM). However 5-fluorouracil (IC50: 30 μM) showed antagonistic effects with respect to other drugs. Additionally, having applied the three drugs in combination on the MCF-7 cell line for the first time in literature, it is highly possible to assess the application of doxorubicin, 5-fluorouracil and propranolol combination as a novel therapy option.
文摘Background: Infantile haemangioma is the commonest childhood tumor. Several lines of treatment are available. Recent reports have focused on the value of propranolol in treating rapidly proliferating haemangioma. The aim of this study was to assess oral propranolol in treatment for facial haemangioma. Patients and Methods: Fifteen patients with rapidly proliferating infantile facial haemangioma with cosmetic disfigurement were treated with oral propranolol. All patients had cardiovascular pre-treatment work-up and commenced on oral propranolol at 3 mg/kg/day. Results: A rapid decrease in hemangioma proliferation was seen in 100% of patients and significant regressions occuring in all patients. This treatment was well tolerated and had little side effects. Conclusions: Oral propranolol is a reliable and easily reproducible method for treatment of facial hemangioma.
文摘Infantile hemangioma and burn hemangioma have many similarities in clinical pictures, pathology and treatment. As infantile hemangioma appears usually after birth and then rapidly grow within few months and then a statue state and then involutes within few years while burn hemangioma so called burn pyogenic granuloma usually appears within days after burn with liquid and grow rapidly into many giant angiomatous masses and then after short time usually weeks or months will involute in more than 37.5% of cases. Hence burn hemangioma and infantile hemangioma sharing many similar features as both are angiomatous with dramatic rapid proliferation of blood vessels that followed by involution but with different time periods and both carry CD133 and CD34 for infantile hemangioma and CD34 for burn hemangioma. Also infantile hemangioma rapidly responds to systemic propranolol and similarly do in cases of burn hemangioma. Accordingly it is more better scientifically to call scalded pyogenic granuloma burn hemangioma. The objective of the present report is to review these conditions and do comparison between them and also to record 6 cases of burn hemangioma and its effective therapy with oral propranolol.
文摘Kaposi’s sarcoma (KS) in Iraq has been reported as sporadic cases of elderly of Iraqi population but after exposure to depleted uranium radiation in early 1991, the frequency of the disease is increasing appearing in younger age with more wide spread and aggressive in nature. There is no satisfactory oral treatment to control this disease. The aim of the present work is to record a new regime of therapy using oral zinc sulfate and oral propanolol. Four patients with wide spread Kaposi’s sarcoma (KS) were treated with oral and topical zinc sulfate solution and oral propranolol. The duration of treatment was between 6 - 12 months and the response started few weeks and was obvious after one month. Most old lesions were resolved leaving post inflammatory hyperpigmentation and few lesions appeared during course of treatment.
文摘The effects of l-, d- and dl-propranolol on antipyrine metabolism and isoprenaline-induced tachycardia were studied in rabbits. The plasma concentration of antipyrine was assayed by Brodie’s spectrophotometric method and the change of heart rate was evaluated by ECG. Both isomers of propranolol hydrochloride were administered iv （800 μg/kg） to the rabbits. d-propranolol produced an antipyrine t 1/2 of 2.67±0.77h and a cl of 0.49±0.1 l/h while its levo-form produced an antipyrine t 1/2 of 1.7±0.39h and a cl of 0.88±0.22 l/h. The differences between the half-lives and between the clearances were statistically significant （P【0.05 for t 1/2, P【0.01 for cl）. The inhibitory effects of l- and d-propranolol on isoprenaline-induced tachycardia were assessed. l-propranolol yielded an ID<sub>50</sub> which was only 1/88 of d-propranolol’s. Our studies showed that the β-receptor blocking activity of propranolol mainly came. from its levoform while the effect on antipyrine metabolism came from its dextro-form.
文摘Epistaxis is a common complaint which is rarely life-threatening, as most cases are self-limited and as such unreported. However, it may be a significant cause for concern if it becomes recurrent. Although a number of medications including topical antihistamines and non-steroidal anti-inflammatory drugs are known aetiological factors for epistaxis due to their antiplatelet effects, beta blockers are not being widely reported as a possible cause. This report presents the case of a 34-year-old G2P0+1, who was diagnosed with hyperthyroidism in pregnancy and subsequently reported epistaxis twice at different occasion and different hospital settings when propranolol was introduced for her treatment, with resolution of epistaxis after withdrawal of propranolol. The report aims to highlight and sensitize physicians to the possible risk of bleeding in patients placed on beta blockers especially propranolol for a wide range of medical condition due to its thrombocytopathic effect.
基金Supported by the National Natural Science Foundation of China, No. 30225047
文摘AIM: To study the stereoselectivity of phase Ⅱglucuronidation metabolism of side-chain propranolol in Chinese Hah population.METHODS: Sixteen adult Chinese Hah volunteers with an average age of 20 years were given a single oral dose of 20 mg racemic propranolol. Human urine at indicated time after administration was collected and S-(-)-propranolol glucuronide and R-(+)-propranolol glucuronide were determined simultaneously by using RP-HPLC.RESULTS: The mean values of kwere 0.19±0.04 h-1 and 0.28±0.06 h-1, of t1/2 3.56±0.73 h and 2.45±0.50 h, of Tmax 2.21±0.45 and 1.75±0.33 h, and of Xu0-24 5.65±0.98 and 2.95±0.62 μmoL for S-(-)- and R-(+)-propranolol glucuronide, respectively. The cumulative excretion percentages in urine of doses were 14.7±2.46% and 7.68±1.60% for S-(-)- and R-(+)-propranolol glucuronide,respectively. The results showed the elimination rate constant kof S-(-)-propranolol glucuronide was less than that of R-(+)-propranolol glucuronide; and the elimination half-life (t1/2), Tmax and the cumulative excretion amount (Xu0-24) of R-(+)-propranolol glucuronide were significantly less than that of S-(-)-propranolol glucuronide.CONCLUSION: The propranolol glucuronidation of the side-chain undergoes stereoselective excretion in Chinese Han population after an oral administration of racemic propranolol.
文摘Objective: This study was originally designed to observe the effects of propranolol (a β-blocker) and Zhigancao Decoction (炙甘草汤 ZGCD) on bone mass in ovariectomized rats. Methods: Thirty-eight female Sprague-Dawley rats were divided into four groups initially, a sham-operated group (Sham, n=7), a model ovariectomized (OVX) group (Model, n=7), a propranolol group (Pro, n=12) and a ZGCD group (ZGCD, n=12). After 15 weeks of treatment, the expected effects were not found. In order to verify the situations of the experiment, we modified the study by administering calcitonin to a subgroup of the tested Pro and ZGCD rats. Results: The Pro and ZGCD treatments showed decreased heart rate and plasma norepinephrine level, but neither an increased bone mass nor any bone metabolism differences from the model rats were found. However, the OVX-induced bone loss was prevented by the sequent treatment of calcitonin. Conclusions: The results provide no evidence that the β-blocker propranolol may stimulate bone formation, and do not justify its use for clinical treatment of osteoporosis.
